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From mold and dirt to drugs, antibiotics have transformed medicine

“Miracle drugs” led to antibiotic resistance.

The Covid-19 pandemic has raised public consciousness about how viruses mutate over time. Many people understand that antibiotics are not effective against viruses but may not be aware that bacteria resist antibiotics like viruses resist vaccines.

Rutgers scientist Selman Waksman, who discovered streptomycin, defined an antibiotic as “a compound made by a microbe to destroy other microbes.” Many of those destroyer microbes have been found in molds and soil.

The discovery of Penicillium notatum in 1928 started a “golden age” of natural product antibiotic discovery.

Antibiotics are compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing microbial species. This phenomenon has long been known; it may explain why the ancient Egyptians had the practice of applying a poultice of moldy bread to infected wounds.

Pathologists at Oxford University focused on purifying Penicillium notatum. The advent of World War II added urgency to turn the mold into a life-saving drug. By 1940, their experiments demonstrated that penicillin could protect mice against a “strep” infection.

The scientists administered penicillin to the first human patient on 12 February 1941. While gardening, a 43-year old policeman got a scratch while pruning roses which led to his “life-threatening infection.” After an Oxford penicillin injection, he began to recover but died when the supply of the new drug was exhausted.

Britain partnered with the U.S. to find a way to mass produce penicillin in the midst of WWII.

The advent of penicillin as a clinical and commercial reality depended on a wide range of biological, scientific, and human resources operating in an open network. Arguing that penicillin would play a critical role in the recovery of manpower, US military leaders mobilized these resources instead of prioritizing economic goals. Mold samples, top-secret reports, and scientists began flying all over the country and, in some cases, the world. This approach induced collaboration among the varied scientists involved with the wartime project, providing them access to a previously unfathomable network of scientific exchange.

Although several companies tackled the challenge, “most of the penicillin that went ashore with Allied forces on D-Day came from” Charles Pfizer & Co. [now simply Pfizer].

The then-small chemical company had made citrus acid since 1880 from unripe citrus imports. When World War I put a crimp in imports, the company hired a food chemist who developed a fermentation process that would eventually “[outpace] the production from lemons and limes.”

It was this innovation that led Pfizer to its method of mass production for penicillin.

After WWII, Pfizer launched a  worldwide soil collection and testing program in its “determin[ation] to find the next miracle medicine.” Dr. Ben Sobin, Pfizer research scientist:

We got soil samples from cemeteries, we had balloons sent up in the air collecting soil samples that were wind blown, we got soil samples from the bottom of mine shafts, we got soil from the  bottom of the ocean. We got soil from the desert; we got it from the tops of mountains, and the bottoms of mountains and in between.

The wide net worked.

In 1949, Pfizer isolated a new antibiotic, Terramycin®, from Indiana soil. It was the first antibiotic developed exclusively by Pfizer scientists and led to a change in the company’s business model. Rather than develop a manufacturing method to license to other companies, Pfizer decided to go retail. Terramycin® was first pharmaceutical Pfizer sold under its own name.

The US Food and Drug Administration approved Terramycin® on 15 March 1950.

Waksman had focused his research on soil-dwelling actinomycetes, leading to the discovery of neomycin and streptomycin, the first treatment for tuberculosis. He received the Nobel Prize for medicine in 1952.

Waksman’s work initiated the Golden Age of antibiotic discovery” whereby antibiotic-producing organisms found in soil led to new microbial natural products (NPs) almost every year. These NPs “are unrivaled in their chemical diversity and effectiveness as antibiotics.”

With such rapid discovery and societal euphoria at being able to treat bacterial infections, from 1944 to 1972 human life expectancy increased by eight years. As with most things in life, moderation is the key. But moderation was not our practice.

According to a 2006 article in the Canadian Journal of infectious Diseases & Medical Microbiology:

Transferable resistance was first identified in Japan in the 1950s…Within two to three years after the introduction of a new antibiotic treatment, resistance usually develops…

And Fleming had foreseen this possibility in 1945:

The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out which can be passed to other individuals and from them to others until they reach someone who gets a septicaemia or pneumonia which penicillin cannot save.

In 2017, the World Health Organization called on factory agriculture to stop using antibiotics in healthy animals.

A systematic review published today in The Lancet Planetary Health found that interventions that restrict antibiotic use in food-producing animals reduced antibiotic-resistant bacteria in these animals by up to 39%…

WHO strongly recommends an overall reduction in the use of all classes of medically important antibiotics in food-producing animals, including complete restriction of these antibiotics for growth promotion and disease prevention without diagnosis. Healthy animals should only receive antibiotics to prevent disease if it has been diagnosed in other animals in the same flock, herd, or fish population.

Yet today, when antibiotic research is essential due to resistance, “most of the large pharmaceutical companies have left the field of NP discovery, and this work is now chiefly undertaken by academic labs and small to medium-sized companies.”

Switching back to vaccines, before 2020 Germany’s BioNTech was “a relatively little-known biotechnology company.” BioNTech, established in 2008 by a husband-wife duo, had been working on an mRNA flu vaccine with Pfizer when Covid-19 hit.

The two companies paired to work on a vaccine for Covid-19.  From MarketWatch:

“We believe that by pairing Pfizer’s development, regulatory and commercial capabilities with BioNTech’s messenger RNA, or mRNA, vaccine technology and expertise as one of the industry leaders, we are reinforcing our commitment to do everything we can to combat this escalating pandemic, as quickly as possible,” said Mikael Dolsten, Pfizer’s chief scientific officer, at the time.

BioNTech manufactured the vaccine for clinical trials based on their research with mRNA vaccines.

Penicillin WWII ad
Advertisement for penicillin production from Life magazine, Science Museum, London

#scitech, #society, #medicine  (054/365)

📷 Los Alamos National Laboratory

Daily posts, 2022-2023

By Kathy E. Gill

Digital evangelist, speaker, writer, educator. Transplanted Southerner; teach newbies to ride motorcycles! @kegill

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